# Inhalation Repurposing of An Approved Drug to Treat Severe Asthma

> **NIH NIH R44** · AEON RESPIRE, INC. · 2021 · $276,752

## Abstract

Project Summary
The business objective of Aeon Respire, and the purpose of this SBIR Project, is to execute key
steps towards repurposing niclosamide as a new asthma treatment. The therapeutic rationale
for these studies is based on initial findings that niclosamide inhibits an ion channel that is
pivotal for airway smooth muscle contraction and mucin hypersecretion. Both of these
pathologic processes contribute to airway narrowing and are considered, in addition to
inflammation, as the core features of asthma. Existing medications fail to adequately relieve
airway narrowing in more severe, treatment refractory patients. In particular, the efficacy of
inhaled beta-agonists is compromised at a cellular level by both repeat use desensitization and
the indirect effects of inflammation. Therefore, there is need for new treatment approaches.
TMEM16A is a calcium-activated chloride channel that regulates calcium signaling in the
airways and is required for airway smooth muscle contraction. Niclosamide is an FDA-approved
oral drug originally discovered decades ago and safely used as an anti-helminth. It was recently
identified in a high throughput unbiased screen as a specific TMEM16A inhibitor. Niclosamide
fully relaxes contracted airways via this mechanism and resists desensitization pathways that
undermine the effectiveness of beta-agonists. It also reduces mucin release induced by asthma-
associated activation signals. TMEM16A inhibition with repurposed niclosamide is therefore an
attractive new asthma treatment approach and will benefit from the drug’s established human
safety record. Niclosamide, however, has poor bioavailability and is unlikely to reach TMEM16A
in the airways through oral dosing. The first objective of the project is to reformulate niclosamide
through particle engineering to enable inhaled dosing. The next objective is to use the new
formulation in inhalation studies to confirm the drug reaches its target locally and will open
airways provoked by a contractile agent. Additional studies will establish the pharmacokinetic
and initial toxicologic profile of inhaled niclosamide. These studies are crucial to test the
scientific hypothesis that inhibiting TMEM16A in the airways is a safe and effective approach to
open obstructed airways. They also represent important steps required to move the project
closer to discussions with the FDA, filing an IND and testing in human studies.

## Key facts

- **NIH application ID:** 10139626
- **Project number:** 1R44HL156372-01
- **Recipient organization:** AEON RESPIRE, INC.
- **Principal Investigator:** John Sullivan
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $276,752
- **Award type:** 1
- **Project period:** 2021-01-09 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10139626

## Citation

> US National Institutes of Health, RePORTER application 10139626, Inhalation Repurposing of An Approved Drug to Treat Severe Asthma (1R44HL156372-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10139626. Licensed CC0.

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